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Clozapine (CLZ) has retained its clinical utility in the management of schizophrenia despite the discovery of novel antipsychotics, as it possesses unique efficacy in the setting of treatment resistant schizophrenia while causing minimal extrapyramidal symptoms. However, these benefits are offset by the risk of agranulocytosis and other side effects, and therapeutic drug monitoring (TDM) is routinely recommended for patients undergoing treatment with CLZ. A multitude of approaches for the quantification of CLZ have been developed for different settings such as TDM, quality control of pharmaceutical dosage forms, and toxicology studies. Primarily, these approaches fall under one of three branches of analysis, namely, chromatography, electrochemical analysis, and spectrophotometry. This study provides a scoping review of the recent advances in the methods of quantification for CLZ and highlights the potential utility of novel methods in the field of drug quantification.

The management of hemophilia A has undergone a remarkable revolution, in line with technological advancement. In the recent past, the primary concern associated with Factor VIII (FVIII) concentrates was the risk of infections, which is now almost resolved by advanced blood screening and viral inactivation methods. Improving patients' compliance with prophylaxis has become a key focus, as it can lead to improved health outcomes and reduced health care costs in the long term. Recent bioengineering research is directed toward prolonging the recombinant FVIII (rFVIII) coagulant activity and synthesising higher FVIII yields. As an outcome, B-domain deleted, polyethylene glycolated, single-chain, Fc-fused rFVIII, and rFVIIIFc-von Willebrand Factor-XTEN are available for patients. Moreover, emicizumab, a bispecific antibody, is commercially available, whereas fitusiran and tissue factor pathway inhibitor are in clinical trial stages as alternative strategies for patients with inhibitors. With these advancements, noninfectious complications, such as inhibitor development, allergic reactions, and thrombosis, are emerging concerns requiring careful management. In addition, the recent approval of gene therapy is a major milestone toward a permanent cure for hemophilia A. The vast array of treatment options at our disposal today empowers patients and providers alike, to tailor therapeutic regimens to the unique needs of each individual. Despite significant progress in modern treatment options, these highly effective therapies are markedly more expensive than conventional replacement therapy, limiting their access for patients in developing countries. [ABSTRACT FROM AUTHOR]

Wound healing is a timely and orderly process comprised of coagulation, inflammation, proliferative, and remodeling. Any disruption in the physiological process will delay the healing process and result in chronic wounds. Wound cleansing is the standard management for acute wounds to provide an optimal environment for healing. Besides wound cleansers, topical antimicrobials are commonly used to reduce microbial load and prevent microbial infection. However, they are associated with adverse reactions and antibiotic resistance, resulting in delayed wound healing. To overcome the limitations of conventional wound treatment, herbal therapy as an alternative is implemented for wound management with antimicrobial, anti-inflammatory, and antioxidant properties. Following the increased demands of herbal therapy in wound management, the innovative polyherbal formulation has gained popularity and has been extensively studied to promote better wound healing. The combined use of multiple herbs is comparatively cost-effective in providing synergistic effects with minimal side effects. This review provides insight into the role and mechanism of diverse medicinal plants with wound healing potential for acute wound management. [ABSTRACT FROM AUTHOR]

Cervical cancer (CC) is one of the most common and severe malignant gynaecological tumours affecting women worldwide. It remains a global health burden especially in low- and middle-income countries. In Malaysia, CC is classified as the second most common cancer affecting women following breast cancer. The survival rate of CC in Malaysia is the lowest in Malays, followed by Indians and Chinese. This indicates several factors including age and ethnicity may significantly affect the survival rate among CC patients. Persisting infection with high-risk subtypes of the human papilloma virus (HPV) is the main aetiologic factor for the development of CC in addition to other factors that are involved in the pathogenesis of the disease. Genetic modifications such as loss of heterozygosity, mutation and amplification as well as epigenetic mechanisms such as DNA methylation and histone acetylation have been reported to contribute to CC. Besides, local microbiota and environmental factors including smoking, diet and oxidative stress have been associated with the development and progression of CC. Hormonal dysregulation in CC patients and animal models suggest the role of hormones in cervical carcinogenesis. Increased understanding of CC offers the hope to limit the burden of disease and effective prevention programmes is particularly important as the disease is highly preventable. This article aims to discuss and provide a comprehensive overview on the pathogenesis of CC. [ABSTRACT FROM AUTHOR]

Worldwide epidemic prevention and control remain under significant stress due to the global novel coronavirus disease 2019 (COVID-19) pandemic and the ongoing emergence of variants like Omicron. The total confirmed COVID-19 cases globally as of now topped 620 million, while the total number of fatalities exceeded 6.6 million. The screening, drug discovery, and clinical development of novel treatments are still the hottest subjects in the treatment of COVID-19, and scientists throughout the world are dedicated to identifying prospective therapeutic agents to treat COVID19 patients, including the new uses of old medications. Remdesivir, a COVID-19 therapeutic medication developed by Gilead Sciences, exerts antiviral effects by suppressing the RNA-dependent RNA polymerase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Remdesivir has maintained high inhibitory activity against all existing SARS-CoV-2 variants, including the Omicron variant. We systematically retrieved Web of Science, CNKI, PubMed, and Clinicaltrials.gov to gather information related to Remdesivir on COVID-19 treatment. In this review, we summarized and reviewed the drug targets for COVID-19 management, especially the mechanism of action and research progress of Remdesivir. More importantly, the outcome of current clinical trials of Remdesivir alone and when combined with other drugs for COVID-19 management was analyzed, and the limitations and clinical significance of each clinical trial were evaluated. From this review, we can understand the development progress of Remdesivir for COVID-19 management, deepens the current understanding of Remdesivir research status, and gives us some inspiration for better drug use in COVID-19 management. [ABSTRACT FROM AUTHOR]

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Hypertension is one of the most prevalent non-communicable diseases in the Malaysian population. In addition, it is associated with various mood and psychiatric disorders such as schizophrenia. Recent studies have shown that hypertension leads to worse clinical outcomes in psychiatric patients. Diverse psychosocial factors caused by schizophrenia also impact hypertension and its clinical care. Clozapine and amlodipine are the hallmark drugs for the treatment of schizophrenia and hypertension, respectively. To date, there is no analytical assay that can simultaneously determine the concentrations of these two drugs in human matrices. An Aquasil C18 column was used in the analysis, with the mobile phase consisting of acetonitrile:water (40:60 v/v) adjusted to pH 4.5 with phosphate buffer. Detection with UV spectrometer was done at 240nm. The method was validated according to the International Council for Harmonization (ICH) guidelines. The calibration curves of clozapine and amlodipine were linear in the range of 100-600 ng/mL and 2-12 ng/mL, respectively (r2>0.99). Clozapine limit of detection (LOD) and limit of quantification (LOQ) were 129.5 ng/mL and 392.4 ng/mL, respectively. Meanwhile, amlodipine achieved LOD of 0.25 ng/mL, and LOQ of 0.75 ng/mL. Overall, the study describes quick, precise and sensitive HPLC-UV method for the simultaneous determination of clozapine and amlodipine in human plasma. [ABSTRACT FROM AUTHOR]

Uterine fibroids (UFs) are a common benign gynecological tumor that affect 70-80% of women over their lifetime. Several pharmacological agents are available to reduce the size of fibroids and ameliorate the symptoms of UF. However, these drugs are expensive and are usually associated with profound side effects. Thus, medicinal herbs are gaining attention in this era due to their cost effectiveness with a comparable or more potent therapeutic efficacy while demonstrating lesser adverse effects. Previous studies have extensively explored on the benefits and risks of using medicinal herbs in the treatment of uterine fibroid. However, a detailed review on the mechanism of medicinal herb extracts and polyherbal preparation have not been conducted. The objective of this review is therefore to summarize the available information on the mechanism of various medicinal herbs and polyherbal formulations with anti-uterine fibroid activity. A systematic search was performed using several search engines such as PubMed, Google Scholar, and Science Direct to identify medicinal herbs with anti-uterine fibroid activity. Based on the literatures identified, a total of five medicinal herbs and three polyherbal formulations were included and discussed in this review, which yields useful information regarding the mechanism of different medicinal herbs and polyherbal formulations in exerting anti-uterine fibroid activity for its potential use as an alternative treatment choice for uterine fibroids. [ABSTRACT FROM AUTHOR]

The study aimed to investigate the phytochemical screening and antioxidant potential of a novel polyherbal formulation DM-15, comprising Cucumis sativus L., Momordica charantia and Azadirachta indica. C. sativus, M. charantia and A. indica were blended together and preserved under -80°C for 24 hours. The crystallized DM-15 was obtained from freeze-drying. DM-15 was subjected to phytochemical screening and was tested in vitro antioxidant contents using total phenolics content (TPC) and total flavonoids content (TFC). Its antioxidant activities were also assessed using 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric ion reducing antioxidant power (FRAP) radical scavenging assays. All determinations of antioxidant activities were performed in triplicates. All data were presented as mean ± SD. Analysis of variance and significant difference among means were tested by one-way ANOVA followed by Tukey's multiple comparison test. Statistical significance was accepted with (P < 0.05), indicating significant difference and 95% of confidence intervals. Statistical analysis was performed using Prism software. Preliminary phytochemical screening showed the presence of alkaloids, flavonoids, saponins, sterols and cardiac glycosides. According to ABTS, the half maximal inhibitory concentration (IC50) values of ascorbic acid (AA), trolox and DM-15 were 1.50 ± 1.15 µg/ml, 0.78 ± 0.06 µg/ml and 92.46 ± 1.78 µg/ml respectively. For DPPH, the IC50 values were 2.57 ± 1.02 µg/ml, 6.85 ± 2.32 µg/ml and 1007.33 ± 4.04 µg/ml for AA, trolox and DM-15 respectively. The FRAP values equivalent to 1 µM FeSO4 of AA, trolox and DM-15 were 52.76 ± 6.46 µg/ml, 53.28 ± 1.28 µg/ml and 22125.07 ± 41.88 µg/ml respectively. TFC of DM-15 was 2.56 ± 0.39 mg of RU/g whereas the TPC value was 10.23 ± 0.20 mg GAE/g. The antioxidant capabilities of the polyherbal DM-15 were ascertained. Knowing the antioxidant properties DM-15, further investigation suggested to investigate its roles in various ailments including cancer and diabetes mellitus. [ABSTRACT FROM AUTHOR]

The widely reported adverse effects of synthetic ingredients encourage the development of green cosmeceuticals to achieve Sustainable Development Goal (SDG) 3. The waste product of mangosteen (mangosteen peel) was utilized in the formulation to reduce waste production corresponding to SDG 12, in addition to its anti-aging and pigmentation control effects. This study aimed to formulate and evaluate novel herbal face creams containing standardized mangosteen peel extract. The mangosteen creams were formulated using natural ingredients and were evaluated for their organoleptic characteristics, rheology, spreadability and pH. Furthermore, an accelerated stability study, freeze-thaw stability study and centrifugation test were conducted. In addition, 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assays were conducted to assess its antioxidant effects, whereas tyrosinase inhibitory assay was conducted to determine its anti-tyrosinase activity. The formulated creams appeared light yellowish-brown and homogenous without phase separation. The creams displayed shear-thinning behavior and optimal pH which was ideal for topical application. The creams were stable after being subjected to various stability tests and were shown to have antioxidant and anti-tyrosinase activity. In conclusion, the development of mangosteen-based green cosmeceutical face cream is in line with SDG 3 and 12. It is expected to be used as a safe and effective alternative to synthetic products. [ABSTRACT FROM AUTHOR]

Free radicals have been associated with the aetiology of many chronic illnesses. Thus, there is an increased need to identify potent antioxidants which can significantly destroy the free radicals. Combination of multiple herbs in polyherbal formulations (PHF) is often associated with greater therapeutic efficacy due to synergism. However, antagonism can occur in natural product mixtures and the resultant antioxidant potential might not always be the additive value of antioxidant properties of each component. The study aimed to evaluate the antioxidant capacity and interaction among the herbs in TC-16, a new PHF comprising Curcuma longa L., Zingiber officinale var. Bentong, Piper nigrum L., Citrofortunella microcarpa (Bunge) Wijnands and Apis dorsata honey. TC-16 was tested for the presence of phytochemicals followed by the determination of phenolic and flavonoid contents. The antioxidant properties of TC-16 and its ingredients were assessed using in vitro antioxidant assays (ABTS, DPPH, FRAP, ORAC, and β-carotene bleaching (BCB) assays). The difference in antioxidant activity and combination index were calculated to study the interactions among the herbs. Alkaloids, flavonoids, steroids, saponins, and glycosides were present in TC-16. TC-16 possessed the highest contents of phenolics (46.14 ± 1.40 mg GAE/g) and flavonoids (132.69 ± 1.43 mg CE/g) after C. longa. Phenolics and flavonoids are well-known antioxidant components that have been reported for their potential health benefits and prevention of diseases. The antioxidant mechanism of TC-16 was mainly by hydrogen atom transfer (HAT), a concerted movement of a proton and an electron in a single kinetic step. Synergism was reported in the antioxidant activity of TC-16 evaluated by ORAC and BCB assays while other assays have demonstrated antagonism. TC-16, a PHF comprising five herbs revealed that HAT is the main mechanism contributing to its antioxidant activity. Free radicals damage is associated with the development of many chronic health disorders. Hence, the antioxidant potential demonstrated by TC-16 could be beneficial in addressing this situation. A future study investigating the interaction of these herbs in combating cancer-related diseases is highly warranted, due to the multifactorial pathogenesis of cancer, which can be addressed by PHF that can act through multiple pathways. [ABSTRACT FROM AUTHOR]

In Malaysia, all pharmacy graduates are required to undergo a one-year Provisionally Registered Pharmacist (PRP) training in either private or public premises. Due to lack of a comprehensive, nationwide study that covers both public and private of training for the PRP, including government hospital, private hospital, government health clinic, community pharmacy, manufacturing pharmaceutical industry, non-manufacturing pharmaceutical industry, research, and development (academia), a nationwide study is conducted. This study aims to assess the course satisfaction and perception of Malaysian Provisionally Registered Pharmacist towards their training in different settings. A crosssectional nationwide study was conducted among Malaysian PRP who started their PRP training at least 6 months ago and those who finished their PRP training within the past 2 years using a self-administered questionnaire. A total of 255 PRPs participated in the survey. On the basis of the response received, most of the respondents felt that the oneyear training period was sufficient. More than 30% of the respondents from government sectors opined that the logbook is too complicated and some logbook requirements are hard to achieve. Most of the respondents are required to do extended hours except for the pharmaceutical industry. In conclusion, most of the respondents were satisfied with the PRP training in Malaysia. However, there is still some inconsistency of quality in PRP training programs in different settings such as the lack of important facilities on certain premises. The findings of this study indicate some suggestions and factors that affect PRP's job satisfaction. Hence, this can be used as an indicator for further improvement of current PRP training. [ABSTRACT FROM AUTHOR]

Dysmenorrhea is often being neglected among women with the mindset that it is not life-threatening, treatment is sought only when present signs/symptoms. Previous studies have proven that women with dysmenorrhea are more susceptible to depression and anxiety as a result of menstrual pain. This research aims to study the potential therapeutic effect of MM-15 polyherbal formulation on chronic dysmenorrhea-associated mood disorders. Adult female ICR mice were employed in this study. Sixty non-pregnant mice were randomly grouped into six groups: estrogen + normal saline group; estrogen + oxytocin group; estrogen + oxytocin + purified water group; estrogen + oxytocin + MM-15 group (50mg/kg p.o.); estrogen + oxytocin + MM-15 group (100mg/kg p.o.); estrogen + oxytocin + MM-15 group (200mg/kg p.o.). Open field test (OFT), social interaction test (SIT) and tail suspension test (TST) were employed to measure the effect of MM-15 formulation on chronic dysmenorrhea-induced mood disorders. From the analyzed result, high dose of MM-15 formulation (200mg/kg, p.o.) increased the total distance travelled in OFT which indicated significantly reduction in anxiety-like response. In TST, the same dose of MM-15 formulation significantly showed potential antidepressant response by reducing immobility time. In SIT, all dose of MM-15 formulation does not improve social-withdrawal behavior in mice with chronic dysmenorrhea. Overall, MM-15 polyherbal formulation has a significant result in reducing chronic dysmenorrhea-induced mood disorders in mice, including depressive and anxiety-like behaviours. [ABSTRACT FROM AUTHOR]